Is there hope for containment by drugs and vaccines?

Current Research on Ebola Treatments

Under a magnification of 25,000X, this digitally-colorized scanning electron bola continues to micrograph (SEM) depicts numerous plague West Africa as filamentous Ebola virus particles (red) E budding from a chronically-infected it infringes upon the USA. VERO E6 cell (blue). From the NIAID. Meanwhile, there is a scrambleA to develop and specific to the proteins of approve new treatment Ebola. The antibodies are options for this deadly designed to disease. bind and neutralize the Ebola virus. ZMAPP has been used By Christopher Massey Several promising on an emergency basis to treat November, 2014 vaccinations and therapies some victims of Ebola. have been developed over the last couple of decades, but However, due to the limited they have yet to be thoroughly number of doses produced, Christopher Massey is the tested for use in humans. the safety and efficacy of Research and Development Some treatments have been ZMAPP has not been fully Manager at Hardy Diagnostics. tried on human subjects in determined. ZMAPP is emergency situations, but produced in genetically He earned his degree in their safety and efficacy are engineered tobacco plants, microbiology at Cal Poly in still unknown. which makes the production San Luis Obispo, California. of new doses a slow process.

Phase 1 trials are being

HardyDiagnostics.com ZMAPP planned and are expected to start soon. The most widely publicized proposed treatment is ZMAPP. This therapeutic

agent, developed by MAPP Biopharmaceutical, is a chimera of three separate monoclonal antibodies

with Marburg virus were also significant benefit of TEKMIRA protected when BCX-4430 Brincidofovir is that it can be was administered up to 48 taken orally as a tablet and is Tekmira has answered with a hours after infection. This shelf-stable at room cocktail of three siRNAs would make this therapy an temperature, making this a (Small Interfering RNAs) option for people accidentally choice therapy for against Ebola packaged as exposed to the virus. Aside introduction to the third world lipid nanoparticles. These from filoviruses, BCX-4430 if proven effective. lipid nanoparticles supposedly has demonstrated encapsulate the siRNAs and broad-spectrum activity deliver them through the against more than 20 RNA FAVIPIRAVIR bloodstream to target cells, viruses in nine different where they are then families, including filoviruses, Toyama Chemical’s transported into the cell. Once togaviruses, bunyaviruses, Favipiravir was primarily inside the cell, siRNA’s bind arenaviruses, developed as a stockpiled with viral RNA and signal its paramyxoviruses, therapeutic drug against degradation. coronaviruses and influenza outbreaks. The drug, flaviviruses. Phase 1 trials are with a broad spectrum of Tekmira began Phase 1 trials expected to be underway activity against RNA viruses, early this year, and the drug soon. has been proposed for use in has been used on patients on treating Ebola. Its mechanism an emergency basis. The drug of action is through selective has been shown to be 100% BRINCIDOFIVIR inhibition of viral RNA- effective in monkeys infected dependant RNA polymerase. with a 1995 strain of the Chimerix’s Brincidofivir is Unlike Brincidofovir, there is Ebola Zaire virus. similar, a broad-spectrum no evidence to indicate that antiviral which selectively Favipiravir has any effect on disrupts the viral DNA eukaryotic polymerases. Mice BCX-4430 polymerase complex. This studies have shown 100% drug has shown effectivity recovery of mice infected BioCryst has gone the route of against dsDNA viruses like with Ebola if treated with a broad spectrum anti- cytomegalovirus, adenovirus, Favipiravir within six days of retroviral. BCX-4430 is an BK virus, smallpox, infection. Favipiravir is in RNA polymerase inhibitor, and herpes simplex virus and Phase III trials in the U.S. for which binds to the active site it is in phase III trials against influenza treatment, and used by the viral polymerase cytomegalovirus and Toyama Chemicals states that and becomes incorporated adenovirus. The drug has also they have over 20,000 doses into transcripts, thus been shown effective in vitro of the drug stockpiled for use. disrupting transcription via against Ebola (even though chain termination. A Nature the virus is an RNA virus) and paper released in March of has been administered to PLASMA TRANSFUSION this year showed that BCX- some patients on an 4430 injected intramuscularly emergency basis. The FDA For a more traditional after infection with Ebola and has approved Phase II trials treatment, blood plasma Marburg virus protected against Ebola to begin in transfusion from recovered rodents. Macaques infected infected patients. One Ebola victims to infected patients has been proposed as altogether. a course of action. A paper Another potential option uses released in 1999 described the NIAID/GSK is working on Vesicular Stomatitis Virus as administration of plasma from two versions of the same a vector to deliver Ebola convalescent Ebola victims to vaccination which uses a non- glycoprotein genes to target eight infected Ebola patients. replicating chimpanzee cells. A major difference Only one of the eight patients adenovirus to deliver one or between this vaccination and died, showing that plasma two Ebola glycoproteins into the NIAID/GSK vaccination transfusion may be a possible human cells. One is for the is that VSV-EBOV is method of treatment. Zaire strain of Ebola; the replication-competent. Studies other is for the Sudan strain as on macaques show that well as the Zaire strain. vaccination may be effective after a single treatment and The adenovirus injection is that the vaccine may be boosted with a modified administered orally or intra- vaccinia virus for immediate nasally, greatly aiding in the and lasting protection. Once deployment of the vaccine to the virus enters the cell, the target areas of low resources. sequence for glycoprotein recombines into the host Antibodies from the DNA, and the cell begins convalescent victim would be producing it. transferred to the patient, which would then fight the When the immune system virus in the patient. The recognizes the Ebola effectiveness of this treatment glycoprotein, it responds with is largely unknown, but it may antibody production and B- serve as a stop-gap treatment cell proliferation, generating until other therapies can be immunity against the virus. properly developed and approved. The use of a human adenovirus was not utilized Similar to the NIAID/GSK due to natural immunity in vaccine, Crucell VACCINES some of the population to the Biopharmaceuticals is adenovirus itself, rendering developing a recombinant While some are developing the vaccination ineffective for adenovirus to deliver treatments for those already some recipients. multiple-vector protection infected, some are working on against Ebola and Marburg vaccines to stop the disease In a challenge study, all four virus. Marburg virus is a macaques given the similar filovirus which causes vaccination showed robust intermittent outbreaks of protection against Ebola virus. hemorrhagic disease in The vaccination is currently in humans. Testing is currently Phase 1 trials for safety which being conducted to determine are expected to complete in the most effective construct. December of 2014. This vaccination is planned for clinical trials in late 2015/early 2016.

While these treatments and vaccines are still in their early stages, it is encouraging that there are several options in development to combat this devastating disease.

Chris Massey Santa Maria, CA